Design of Modern Approaches for the (Asymmetric) Synthesis of Original Fluorinated Molecules

该合作项目旨在开发新型和现代的方法来合成前所未有的氟化分子。氟化基序在有机化学中，即在农业化学和药物活性成分中是重要的。事实上，用新出现的氟化基团取代的目标化合物将通过大大扩展氟化分子的化学空间来实现该领域的新进展，因为迄今为止这是一个未知的研究领域。为了实现这一具有挑战性的目标，设想了两种互补的方法的基础上的非对称阴离子结合（WP 1）和不对称阴离子结合（WP 2）的策略。对于这两种方法，将进行创新的中性和阳离子单/二氟甲基化和二氟甲基硫醇化试剂的设计和合成，为以后开发的催化方法的实施提供所需的平台。因此，在WP 1中，将追求用二氟甲基化和二氟甲基硫代化源选择性地官能化苄基C（sp3）-H键。或者，在WP 2中，将开发使用不同的前手性亲核试剂的对映选择性氟甲基化、二氟甲基化和二氟甲基硫醇化方法，包括亲电阳离子试剂的催化阴离子结合活化。有机氟化学（Besset，合成方法和原始试剂的设计）和光催化或有机催化（García Mancheño，有机光催化剂设计和阴离子结合方法）方面的专业知识相结合，对于应对这一具有挑战性的风险至关重要。AsymFluoChem项目的成功将丰富化学家的工具箱，使其能够使用现代技术合成前所未有的非手性和对映体富集分子。此外，在有机氟化学、有机催化和光化学方面也将有新的发展前景，这在学术界和化学工业应用中都有很大的兴趣。

This collaborative project aims at developing novel and modern approaches towards the synthesis of unprecedented fluorinated molecules. Fluorinated motifs are important in organic chemistry, namely in agrochemical and pharmaceutical active ingredients. Indeed, the targeted compounds substituted with emergent fluorinated groups will allow for new advances in the field by expanding considerably the chemical space of fluorinated molecules as so far this is an uncharted research area. To reach that challenging goal, two complementary approaches based on photocatalysis (WP1) and asymmetric anion-binding (WP2) strategies are envisioned. For both approaches, the design and synthesis of innovative neutral and cationic mono-/difluoromethylating and difluoromethylthiolating reagents will be carried out, providing the required platform for the later implementation in the catalytic methods to be developed. Hence, in WP1 the selective functionalization of benzylic C(sp3)-H bonds with difluoromethylating and difluoromethylthiolating sources will be pursued. Alternatively, in WP2 enantioselective fluoromethylation, difluoromethylation and difluoromethylthiolation methods using different pro-chiral nucleophiles, embracing a catalytic anion-binding activation of electrophilic cationic reagents, will be developed. The combination of the expertise in organofluorine chemistry (Besset, synthetic methodologies and design of original reagents) and photo- or organocatalysis (García Mancheño, organophotocatalysts design and anion-binding methodologies) is essential in tackling this challenging venture. The success of the AsymFluoChem project will enrich the chemist’s toolbox with methods allowing the synthesis of unprecedented both non-chiral and enantioenriched molecules using modern technologies. Furthermore, novel perspectives in organofluorine chemistry, organocatalysis and photochemistry will be developed, which are of great interest in academia and for chemical industry applications.